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British Journal of Radiology (2003) 76, 585-586
© 2003 British Institute of Radiology
doi: 10.1259/bjr/24373060
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Editorial

Why do we need more accurate intraprostatic localization of cancer?

A R Padhani, MRCP, FRCR 1 and C M Nutting, MRCP, FRCR, MD 2

1 The Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN and 2 Department of Radiotherapy, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK

External beam radiotherapy is a key modality in the treatment of patients with prostate cancer. The goal of radiotherapy is to deliver a high radiation dose to tumour-bearing tissues and minimize unnecessary irradiation of surrounding normal tissue structures. This maximizes the chance of tumour eradication and reduces the chance of normal tissue damage. In the treatment of prostate cancer the radiation dose that can be delivered to the prostate gland is often limited because of the potential risk of damage to the adjacent bladder, rectum and small bowel. Early results of clinical trials suggest that an increase in the delivered radiation dose is associated with improved prostate specific antigen (PSA) control [1] and it is hoped that this will translate into improved local control and overall survival in prostate cancer.

Using intensity-modulated radiotherapy (IMRT), complex three-dimensional dose distributions can now be generated to concentrate very high radiation doses in areas of high tumour-cell density within the prostate gland, without significantly increasing the risk of normal tissue injury [2, 3]. IMRT may be used to escalate dose in excess of 80 Gy to the whole prostate gland, with a dose constraint on the anterior rectal wall [4]. To take full advantage of the opportunity of IMRT, imaging techniques that are able to map tumour volume within individual organs are needed [5, 6]. If it were possible to accurately determine the location of intraprostatic tumour nodules within the prostate gland, IMRT may allow dose escalation to these nodules with the aim of increasing tumour control with the benefit of lesser irradiation to surrounding structures [2]. It has been suggested that dynamic contrast enhanced MRI (DCE-MRI) or hydrogen spectroscopy (1H-MRSI) may be able to map functional tumour volume in the prostate gland and thus define the biological tumour volume for irradiation [5].

A number of studies have compared DCE-MRI with spin-echo T2 weighted images in patients with known prostate cancer and have found that there is an advantage in the detection of tumours (Table 1Go) [7–10]. Ogura et al made the specific point that DCE-MRI was more accurate in detecting cancers in the peripheral gland where the overall accuracy rate was 80% compared with transitional zone where tumour detection accuracy was only 63% [10]. The sensitivity and specificity of tumour detection was 81% and 79% for peripheral gland cancers and 37% and 97% for transition zone cancers, respectively [10]. Ito et al who have published an article in this issue of the British Journal of Radiology compared the visualization of prostate cancer with DCE-MRI and transrectal ultrasound (TRUS) with power Doppler using TRUS biopsy as the reference standard [11]. This study shows that the overall sensitivity, specificity and accuracy for cancer visualization with DCE-MRI (87% 74% and 82%, respectively) is better than power Doppler ultrasound (69%, 61% and 66%) but only for peripheral gland tumours. They also noted that reliable detection of transition zone tumours (those without a peripheral gland component) was poorer. However, two studies have noted that it is possible to differentiate between tumour and central gland enhancement [12, 13] using complex pharmacokinetic modelling techniques. Both Engelbrecht et al [12] and Turnbull et al [13] have described significant differences between carcinoma and benign prostatic hyperplasia (BPH) in the amplitude of the initial enhancement. In general, cancers have higher amplitude of enhancement when compared with BPH. Additionally, Engelbrecht et al have recently shown significant differences in the washout patterns between cancers and BPH [12]. These studies taken together suggest a definative role for DCE-MRI for the intraprostatic localization of prostate cancer particularly for peripheral gland tumours where the vast majority arise.


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  		Table 1. Accuracy of dynamic contrast enhanced (DCE)-MRI for the detection of prostate cancer

 
It is also important to remember that localization of aggressive tumour (higher Gleason score or high proliferation rate or hypoxic regions) would bring additional advantages for functional IMRT planning. DCE-MRI has not been shown to be robust in predicting tumour grade [12, 14]. 1H-MRSI appears more promising in this regard [15, 16], but high resolution 1H-MRSI can only be achieved with the use of an endorectal coil [17]. Inherent prostate gland distortion associated with endorectal coil usage will have to be taken into account if 1H-MRSI is to be used for planning IMRT.

References

  1. Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, et al. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 2002;53:1097–105.[CrossRef][Medline]
  2. Nutting CM, Corbishley CM, Sanchez-Nieto B, Cosgrove VP, Webb S, Dearnaley DP. Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy. Br J Radiol 2002;75:151–61.[Abstract/Free Full Text]
  3. Leibel SA, Fuks Z, Zelefsky MJ, et al. Intensity-modulated radiotherapy. Cancer J 2002;8:164–76.[Medline]
  4. Zelefsky MJ, Fuks Z, Happersett L, et al. Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer. Radiother Oncol 2000;55:241–9.[CrossRef][Medline]
  5. Ling CC, Humm J, Larson S, et al. Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys 2000;47:551–60.[CrossRef][Medline]
  6. Rosenman J. Incorporating functional imaging information into radiation treatment. Semin Radiat Oncol 2001;11:83–92.[CrossRef][Medline]
  7. Jager GJ, Ruijter ET, van de Kaa CA, et al. Dynamic TurboFLASH subtraction technique for contrast-enhanced MR imaging of the prostate: correlation with histopathologic results. Radiology 1997;203:645–52.[Abstract/Free Full Text]
  8. Namimoto T, Morishita S, Saitoh R, Kudoh J, Yamashita Y, Takahashi M. The value of dynamic MR imaging for hypointensity lesions of the peripheral zone of the prostate. Comput Med Imaging Graph 1998;22:239–45.[CrossRef][Medline]
  9. Tanaka N, Samma S, Joko M, et al. Diagnostic usefulness of endorectal magnetic resonance imaging with dynamic contrast-enhancement in patients with localized prostate cancer: mapping studies with biopsy specimens. Int J Urol 1999;6:593–9.[CrossRef][Medline]
  10. Ogura K, Maekawa S, Okubo K, et al. Dynamic endorectal magnetic resonance imaging for local staging and detection of neurovascular bundle involvement of prostate cancer: correlation with histopathologic results. Urology 2001;57:721–6.[CrossRef][Medline]
  11. Ito H, Kamoi K, Yokoyama K, Yamada K, Nishimura T. Visualization of prostate cancer using dynamic contrast-enhanced MRI: comparison with transrectal power Doppler ultrasound. Br J Radiol 2003;76:617–24.[Abstract/Free Full Text]
  12. Engelbrecht MR, Huisman HJ, Laheij RJ, et al. Discrimination of peripheral zone and central gland prostate cancer from normal prostatic tissue using dynamic contrast-enhanced MR imaging. Radiology 2003; accepted.
  13. Turnbull LW, Buckley DL, Turnbull LS, Liney GP, Knowles AJ. Differentiation of prostatic carcinoma and benign prostatic hyperplasia: correlation between dynamic Gd-DTPA-enhanced MR imaging and histopathology. J Magn Reson Imaging 1999;9:311–6.[CrossRef][Medline]
  14. Padhani AR, Gapinski CJ, Macvicar DA, et al. Dynamic contrast enhanced MRI of prostate cancer: correlation with morpholo55:99–109.
  15. Vigneron DB, Males R, Hricak H, Noworolski S, Carrol PR, Kurhanewicz J. Prostate cancer: correlation of 3D MRSI metabolite levels with histologic grade. Radiology 1998;(P):181.
  16. Zakian K, Sircar K, Kleinman S, Shukla-Dave A, Kattan M, Hricak H. Correlation of proton MR spectroscopic imaging with Gleason score based on step section radical prostatectomy. Radiology 2002;225(P):1525.
  17. Kurhanewicz J, Swanson MG, Nelson SJ, Vigneron DB. Combined magnetic resonance imaging and spectroscopic imaging approach to molecular imaging of prostate cancer. J Magn Reson Imaging 2002;16:451–63.[CrossRef][Medline]



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